Anabolic response of some tissues to diabetes

Abstract

In contrast to liver, adipose tissue, and muscle, in which the diabetic state is associated with a "catabolic response," some tissues, typically the kidney and perhaps the intestinal mucosa and some vascular cell types, show an "anabolic response" to diabetes, with enhanced activity of the anabolic pathways and diminished activity of the catabolic ones. The kidney of alloxan or streptozotocin diabetic rats is hypertrophied, and shows enrichment in intracellular glycogen and abundant accumulation of glycoprotein material at the basement membrane level. Accordingly, protein synthesis and the enzymes of glucose utilization as well as those engaged in UDP sugar formation or in the hydroxylation and glycosylation processes (required for glycoprotein synthesis) show increased activity in the diabetic kidney, while the catabolic, lysosomal enzymes (cathepsin D and several glycosidases) are depressed. We observed a reduction of -24% in the activity of cathepsin D and -23% in that of galactosidase in the kidney of streptozotocin diabetic mice, as opposed to increases of +135 and +32%, respectively, found in liver. It is not known which factor(s) may be responsible for such an anabolic response of some tissues to diabetes, but persistent hyperglycemia and/or some hormonal abnormalities may be involved. The above data refer to changes in tissue enzyme content caused by induction-repression mechanisms, but rapid (activation-inhibition) effects may also occur. We observed that preincubation of slices of mouse kidney cortex for 10 min with 20.8 mmole/liter glucose resulted in a 80% activation of phosphofructokinase, as assayed in the tissue homogenate at physiological (50 mumole/liter) concentration of the substrate fructose-6-P, suggesting that hyperglycemia may be responsible for some of the metabolic changes occurring in the diabetic kidney.